Search

This study aimed to estimate the hepatic and immune ameliorating potential of extracted bovine lactoferrin (LF), Selenium nanoparticles (SeNPs) or their combination (LF/SeNPs) against bleomycin (BLM) induced hepatic injury. Fifty adult male rats (160-200 g) were equally divided into five groups: (1) the saline control group, (2) BLM-injected (15 mg/kg twice a week, ip), and (3-5) groups treated orally with LF (200 mg/kg/day), SeNPs (0.0486 mg/kg/day) or LF/SeNPs combination (200.0486 mg/kg/day) for 6 weeks post BLM-intoxication. Blood and liver samples were subjected to biochemical, histopathological, and immunohistochemical analyses. The results revealed that BLM caused a significant increase in hepatic lipid peroxidation and nitric oxide, as well as serum markers of liver functions (AST, ALT and GGT activities), and levels of GM-CSF, CD4, TNF-α, IL-1β, TGF-β1, fibronectin, triglycerides, cholesterol and LDL-C. Additionally, hepatic glutathione, Na + /K + -ATPase, and glutathione peroxidase, as well as serum HDL-C, total protein and albumin levels were significantly reduced. Moreover, BLM injection resulted in marked histopathological alterations and severe expression of caspase 3. Post-treatment of BLM-intoxicated rats with LF, SeNPs or LF/SeNPs combination obviously improved the BLM-induced hepatic damages; this was achieved from the marked modulations in the mentioned parameters, besides improving the histopathological hepatic architecture. It is worth mentioning that LF/SeNPs exerted the greatest potency. In conclusion, the obtained results demonstrated that LF, SeNPs and LF/SeNPs succeeded in attenuating the BLM-induced hepatic dysfunction. Therefore, these supplements might be used to protect against drug-associated side effects., (© 2024. The Author(s).)

It is known that human milk (HM) 1 antimicrobial protein composition varies during lactation. However, the impact of maternal diet on these antimicrobial proteins, particularly lactoferrin and lysozyme remains unknown. In addition, it is unclear whether daily, circadian, and between breast variations exist for lactoferrin and lysozyme concentrations. We investigated the impact of a low sugar, low fat, high fibre dietary intervention on HM lysozyme and lactoferrin concentrations. HM was sampled across a 3-week period; daily, at different times of day, and from both breasts to measure the level of intraindividual variation. The intervention significantly reduced maternal sugar, total fat, and saturated fat intake. HM lactoferrin concentration declined significantly over the course of the intervention however the effect size was relatively small. In addition, lactoferrin and lysozyme concentrations were variable over time, and differed significantly within and across the day but not between breasts., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Donna Geddes reports financial support was provided by Medela AG. Matthew Payne reports financial support was provided by National Health and Medical Research Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. DTG. declares participation in the Scientific Advisory Board of Medela AG. LFS, ZG, XJ, CTL and DTG are supported by an unrestricted research grant from Medela AG, administered by The University of Western Australia. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. All other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Human lactoferrin (hLf) is an innate host defense protein that inhibits microbial H + -ATPases. This protein includes an ancestral structural motif (i.e., γ-core motif) intimately associated with the antimicrobial activity of many natural Cys-rich peptides. Peptides containing a complete γ-core motif from hLf or other phylogenetically diverse antimicrobial peptides (i.e., afnA, SolyC, PA1b, Pv D 1 , thanatin) showed microbicidal activity with similar features to those previously reported for hLf and defensins. Common mechanistic characteristics included (1) cell death independent of plasma membrane (PM) lysis, (2) loss of intracellular K + (mediated by Tok1p K + channels in yeast), (3) inhibition of microbicidal activity by high extracellular K + , (4) influence of cellular respiration on microbicidal activity, (5) involvement of mitochondrial ATP synthase in yeast cell death processes, and (6) increment of intracellular ATP. Similar features were also observed with the BM2 peptide, a fungal PM H + -ATPase inhibitor. Collectively, these findings suggest host defense peptides containing a homologous γ-core motif inhibit PM H + -ATPases. Based on this discovery, we propose that the γ-core motif is an archetypal effector involved in the inhibition of PM H + -ATPases across kingdoms of life and contributes to the in vitro microbicidal activity of Cys-rich antimicrobial peptides.

The aim of this research was to evaluate the effects of postpartum day and parity season on the lactoferrin (LF), immunoglobulin G (IgG), and chemical composition of Murciano-Granadina goat colostrum during the first 96 h after kidding, and the use of the Brix refractometer to estimate IgG content. A herd of 3500 intensively managed Murciano-Granadina dairy goats (45-50 kg body weight) was used. Colostrum samples were collected from days 1 to 4 postpartum in the winter, spring, summer, and autumn. The colostrum composition was assessed using an automated infrared method; the LF and IgG concentrations were measured using an ELISA, and for the Brix percentage, we used a digital refractometer. Colostrum taken on the first postpartum day showed the highest concentrations of LF, IgG, proteins and non-fat solids (NFSs). As the postpartum days progressed, a rapid decrease in the LF, IgG, protein, and NFS contents and the Brix value was observed. In contrast, the lactose content increased steadily until the fourth postpartum day ( p < 0.001). The season influenced milk yield, LF, IgG, protein, fat, and somatic cell content ( p < 0.05). LF contents were significantly higher in the spring season, IgG contents were higher in autumn colostrum, and fat components were higher in the winter season. The colostrum Brix value showed a positive correlation with the ELISA colostrum LF (r = 0.716, p < 0.001) and IgG (r = 0.894, p < 0.001) determination; a 20 mg IgG/mL colostrum concentration corresponded to 18 °Brix. Our results corroborate the importance of feeding colostrum to newborns on the first day after birth, not only because of its high level of IgG but also because of its greater presence of the other bioactive protein compounds such as lactoferrin.

Background: Curcumin is widely known for its antioxidant and anti-inflammatory properties, but its mechanism of action in mitigating oxidative stress injury in brain vascular endothelial cells remains unclear. Due to the poor bioavailability of curcumin, it is challenging to achieve effective concentrations at the target sites. Nano-micelles are known for their ability to improve the solubility, stability, and bioavailability of hydrophobic compounds like curcumin. This study investigated the effects and mechanisms of free curcumin and curcumin embedded in nano-micelles (M(Cur)) on oxidative stress-induced injury in bEnd.3 cells., Results: At a protective concentration of 10 μg mL -1 , micellar curcumin was better able to recover the morphology of bEnd.3 cells under oxidative stress while increasing cell viability, restoring mitochondrial membrane electrical potential, and effectively inhibiting reactive oxygen species generation with a positive cell rate of 2.21%. These results indicate that curcumin significantly improves H 2 O 2 -induced oxidative stress damage in endothelial cells by maintaining the cellular antioxidant balance., Conclusion: This study adds to knowledge regarding the role of nano-micelles in curcumin intervention for endothelial cell oxidative damage and provides insights for the development of curcumin-based dietary supplements. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Objectives: The aim was to assess the associations between the LTF, MMP20, CA6, and TAS1R2 polymorphisms and caries in the Zhuang population and explore the underlying mechanism of the impact of lactoferrin on caries susceptibility., Methods: A case-control study of 315 adolescents was conducted in Guangxi, China, from May-November 2022. Data were collected through oral examinations and questionnaires. Buccal mucosa cells and DNA samples were collected using the SNPscan technique. Saliva and supragingival plaque samples were taken from 69 subjects with various LTF rs10865941 genotypes. The relationships among the LTF rs10865941 polymorphism, lactoferrin, Streptococcus mutans, and caries were investigated by using the ELISA and qRT-PCR, along with logistic regression analysis., Results: The genotype distribution of the LTF gene were significantly different between the case and control groups (p = 0.018). The case group had lower C allele and greater T allele frequencies than the control group (p = 0.006). The LTF rs10865941 polymorphism was associated with caries in the codominant, dominant, and additive models (p < 0.05). MMP20 rs1784418, CA6 rs2274328, and TAS1R2 rs35874116 were not significantly different between the two groups (p > 0.05). A greater quantity of S. mutans. in the supragingival plaque was found in the case group (p = 0.03). There were significant differences between the two groups in both the codominant model and the dominant model (p < 0.05)., Conclusions: The LTF rs10865941 polymorphism may be associated with caries susceptibility in the Zhuang population of China. The LTF rs10865941 T allele may be a potential risk factor for dental caries., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lactoferrin (Lf) is a multifunctional protein in the transferrin family. It is involved in many physiological functions, including the regulation of iron absorption and immune response. It also has antibacterial, antiviral, anti-inflammatory, anticancer and antioxidant capabilities under pathophysiological conditions. The mammalian lactoferrin receptor (LfR) plays a key role in mediating multiple functions of Lf. Studies have shown that Lf/LfR is abnormally expressed in the brain of Parkinson's disease, and the excessive accumulation of iron in the brain caused by the overexpression of Lf and LfR is considered to be one of the initial causes of the degeneration of dopaminergic neurons in Parkinson's disease. On the other hand, a number of recent studies have reported that Lf/LfR has a significant neuroprotective effect on Parkinson's disease. In other words, it seems paradoxical that Lf/LfR has both neurodegenerative and neuroprotective effects in Parkinson's disease. This article focuses on recent advances in the possible mechanisms of the neurodegenerative and neuroprotective effects of Lf/LfR in Parkinson's disease and discusses why Lf/LfR has a seemingly contradictory role in the development of Parkinson's disease. Based on the evidence obtained so far, we believed that Lf/LfR has a neuroprotective effect on Parkinson's disease, while as to whether the overexpressed Lf/LfR is the cause of the development of Parkinson's disease, the current evidence is insufficient and further investigation needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The increasing resistance of Malassezia yeasts against commonly used antifungal drugs dictates the need for novel antifungal compounds. Human lactoferrin-based peptides show a broad spectrum of antimicrobial activities. Various assays were performed to find the optimal growth conditions of the yeasts and to assess cell viability, using media with low lipid content to avoid peptide binding to medium components., Methods: In the current study, we tested the antimicrobial susceptibility of 30 strains of M. furfur that cover the known IGS1 genotypic variation., Results: hLF(1-11) inhibited the growth of all species tested, resulting in minimum inhibitory concentrations (MIC) values ranging from 12.5 to 100 μg/mL. In the combinatory tests, the majority of fractional inhibitory concentration indexes (FIC) for the tested strains of M. furfur were up to 1.0, showing that there is a synergistic or additive effect on the efficacy of the antifungal drugs when used in combination with hLF(1-11)., Conclusion: Results showed that hLF(1-11) could be combined with fluconazole or amphotericin for the antimicrobial treatment of resistant strains, enhancing the potency of these antifungal drugs, resulting in an improved outcome for the patient.

We present a miniaturized, flow-through model for infantile in vitro digestions, following up on our previously published in vitro digestive system for adults. Microfluidic 'chaotic' mixers were employed as microreactors to help emulate the biochemical processing going on in the infantile stomach and intestine. Simulated digestive fluids were introduced into these micromixers, and the mixtures were incubated for 60 min after both the gastric phase and the intestinal phase. The pH of the infantile stomach was set at 5.3, which is higher than that of adults. This leads to entirely different patterns of digestion for the milk protein, lactoferrin, used in our study as a model compound. It was found that lactoferrin remained undigested as it passed through the gastric phase and reached the intestinal phase intact, unlike in adult digestions. In the intestinal phase, lactoferrin was rapidly digested. Our miniaturized, infantile, in vitro digestive system requires much less labor and chemicals than standard approaches, and shows great potential for future automation., Competing Interests: Declaration of competing interest The authors declare that there are no competing financial interests or personal relationships which could be considered as potential competing interests., (Copyright © 2024. Published by Elsevier Inc.)

As the demand for lactoferrin increases, the search for cost-effective alternative proteins becomes increasingly important. Attention naturally turns to other members of the transferrin family such as ovotransferrin. The iron-binding abilities of these proteins influence their characteristics, although the underlying mechanisms remain unclear. This overview systematically summarizes the effects of the iron-binding ability on the fate of food-derived transferrins (lactoferrin and ovotransferrin) and their potential applications. The findings indicate that iron-binding ability significantly influences the structure of food-derived transferrins, particularly their tertiary structure. Changes in structure influence their physicochemical properties, which, in turn, lead to different behaviors in response to environmental variations. Thus, these proteins exhibit distinct digestive characteristics by the time they reach the small intestine, ultimately performing varied physiological functions in vivo . Consequently, food-derived transferrins with different iron-binding states may find diverse applications. Understanding this capability is essential for developing food-derived transferrins and driving innovation in lactoferrin-related industries.

In this study, non-covalent binding mechanism of lactoferrin (LaF)-theaflavin (TF) complex and its functional properties were investigated. Multi-spectroscopic analyses showed that the secondary structure of LaF was altered with increasing TF concentration. The non-covalent binding of TF to LaF resulted in a reduction in the content of the α-helix and β-sheet, as well as a decrease in the fluorescence intensity of LaF. DSC result showed that non-covalent binding of TF improved thermal stability of LaF. Molecular dynamics simulations confirmed that the stable binding of LaF-TF was driven by hydrogen bonding and hydrophobic interactions. Additionally, non-covalent binding of TF increased the antioxidant capacity and emulsifying properties of LaF. Dynamic interfacial tension indicated that the strong interaction between LaF and TF reduced the interfacial tension, but improved the rheological properties of LaF. The functional characteristics of the non-covalent complex was effectively enhanced, paving the way for its potential use in the food industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Lactoferrin, a glycoprotein derived from breastmilk, is recognized for its health benefits in infants and children; however, its protective effects when administered during gestation and lactation against offspring hypertension remain unclear. This study aimed to investigate whether maternal lactoferrin supplementation could prevent hypertension in offspring born to mothers with chronic kidney disease (CKD), with a focus on nitric oxide (NO), renin-angiotensin system (RAS) regulation, and alterations in gut microbiota and short-chain fatty acids (SCFAs). Prior to pregnancy, female rats were subjected to a 0.5% adenine diet for 3 weeks to induce CKD. During pregnancy and lactation, pregnant rats received one of four diets: normal chow, 0.5% adenine diet, 10% lactoferrin diet, or adenine diet supplemented with lactoferrin. Male offspring were euthanized at 12 weeks of age (n = 8 per group). Supplementation with lactoferrin during gestation and lactation prevented hypertension in adult offspring induced by a maternal adenine diet. The maternal adenine diet caused a decrease in the index of NO availability, which was restored by 67% with maternal LF supplementation. Additionally, LF was related to the regulation of the RAS, as evidenced by a reduced renal expression of renin and the angiotensin II type 1 receptor. Combined maternal adenine and LF diets altered beta diversity, shifted the offspring's gut microbiota, decreased propionate levels, and reduced the renal expression of SCFA receptors. The beneficial effects of lactoferrin are likely mediated through enhanced NO availability, rebalancing the RAS, and alterations in gut microbiota composition and SCFAs. Our findings suggest that maternal lactoferrin supplementation improves hypertension in offspring in a model of adenine-induced CKD, bringing us closer to potentially translating lactoferrin supplementation clinically for children born to mothers with CKD.

Antibiotics, often hailed as 'miracle drugs' in the 20th century, have revolutionised medicine by saving millions of lives in human and veterinary medicine, effectively combatting bacterial infections. However, the escalating global challenge of antimicrobial resistance and the appearance and spread of multidrug-resistant pathogens necessitates research into alternatives. One such alternative could be lactoferrin. Lactoferrin, an iron-binding multifunctional protein, is abundantly present in mammalian secretions and exhibits antimicrobial and immunomodulatory activities. An often overlooked aspect of lactoferrin is its proteolytic activity, which could contribute to its antibacterial activity. The proteolytic activity of lactoferrin has been linked to the degradation of virulence factors from several bacterial pathogens, impeding their colonisation and potentially limiting their pathogenicity. Despite numerous studies, the exact proteolytically active site of lactoferrin, the specific bacterial virulence factors it degrades and the underlying mechanism remain incompletely understood. This review gives an overview of the current knowledge concerning the proteolytic activity of lactoferrins and summarises the bacterial virulence factors degraded by lactoferrins. We further detail how a deeper understanding of the proteolytic activity of lactoferrin might position it as a viable alternative for antibiotics, being crucial to halt the spread of multi-drug resistant bacteria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ongena, Dierick, Vanrompay, Cox and Devriendt.)

Since Coronavirus disease 2019 (COVID-19) still presents a considerable threat, it is beneficial to provide therapeutic supplements against it. In this respect, glycoprotein lactoferrin (LF) and lactoferricin (LFC), a natural bioactive peptide yielded upon digestion from the N-terminus of LF, are of utmost interest, since both have been shown to reduce infections of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for COVID-19, in particular via blockade of the virus priming and binding. Here, we, by means of biochemical and biophysical methods, reveal that LF directly binds to the S-protein of SARS-CoV-2. We determined thermodynamic and kinetic characteristics of the complex formation and mapped the mutual binding sites involved in this interaction, namely the N-terminal region of LF and the receptor-binding domain of the S-protein (RBD). These results may not only explain many of the observed protective effects of LF and LFC in SARS-CoV-2 infection but may also be instrumental in proposing potent and cost-effective supplemental tools in the management of COVID-19.

The poor thermal stability of lactoferrin (LF) hinders its bioavailability and use in commercial food products. To preserve LF from thermal denaturation, complexation with other biopolymers has been studied. Here we present the complex formation conditions, structural stability, and functional protection of LF by α-lactalbumin (α-LA). The formation of the LF-α-LA complexes was dependent on pH, mass ratio, and ionic strength. Changing the formation conditions and cross-linking by transglutaminase impacted the turbidity, particle size, and zeta-potential of the resulting complexes. Electrophoresis, Fourier-transform infrared spectroscopy, and circular dichroism measurements suggest that the secondary structure of LF in the LF-α-LA complex was maintained after complexation and subsequent thermal treatments. At pH 7, the LF-α-LA complex protected LF from thermal aggregation and denaturation, and the LF retained its functional and structural properties, including antibacterial capacity of LF after thermal treatments. The improved thermal stability and functional properties of LF in the LF-α-LA complex are of interest to the food industry., (© 2024 The Author(s). Journal of Food Science published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

Chronic low‑grade inflammation defines obesity as a metabolic disorder. Alterations in the structure of gut flora are strongly associated with obesity. Lactoferrin (LF) has a biological function in regulating intestinal flora. The present study aimed to investigate the therapeutic and anti‑-inflammatory effects of LF in obese mice based on intestinal flora. A total of 30 C57BL/6 mice were divided into three groups consisting of 10 mice each. Subsequently, one group was fed a normal diet (Group K), another group was fed a high‑fat diet (Group M) and the remaining group switched from regular drinking to drinking 2% LF water (Group Z2) after 2 weeks of high‑fat diet; all mice were fed for 12 weeks. After the experiment, the mouse blood lipid and lipopolysaccharide levels, levels of inflammatory factors and intestinal tight junction proteins were assessed. Mouse stool samples were analyzed using 16S ribosomal RNA sequencing. The results showed that LF reduced serum total cholesterol, triglycerides and low‑density lipoprotein levels, elevated high‑density lipoprotein levels, suppressed metabolic endotoxemia and attenuated chronic low‑grade inflammatory responses in obese mice. In addition, LF upregulated zonula occludens‑1 and occludin protein expression levels in the intestine, thereby improving intestinal barrier integrity. LF altered the intestinal microbial structure of obese mice, reduced the ratio of Firmicutes and an elevated ratio of Bacteroidota , modifying the bacterial population to the increased relative abundance of Alistipes, Acidobacteriota, Psychrobacter and Bryobacter .

Lactoferrin is widely found in milk and has the ability to bind iron. Previous studies have reported that lactoferrin was effective in the prevention and treatment of acute alcohol-induced liver injury (AALI). Ferroptosis is a recently discovered cell death and is involved in the development of AALI. However, the potential role of lactoferrin in acute alcohol-induced ferroptosis is still unclear. In this study, we observed that lactoferrin (10, 20, and 40 μg/mL) significantly mitigated alcohol (300 mM)-induced injury in vitro. Additionally, lactoferrin (100 and 200 mg/kg BW) significantly alleviated alcohol (4.8 g/kg BW)-induced injury in vivo. Our results showed that lactoferrin inhibited alcohol-induced upregulation of the ferroptosis marker protein ACSL4 and downregulation of GPX4. Meanwhile, lactoferrin treatment successfully reversed the elevated malondialdehyde (MDA) levels and the reduced glutathione (GSH) levels caused by alcohol treatment. These results may indicate that lactoferrin significantly decreased ferroptosis in vivo and in vitro. Lactoferrin has the potential to chelate iron, and our results showed that lactoferrin (20 μg/mL) significantly reduced iron ions and the expression of the ferritin heavy chain (FTH) under FeCl 3 (100 μM) treatment. It was demonstrated that lactoferrin had a significant iron-chelating effect and reduced iron overload caused by FeCl 3 in AML12 cells. Next, we examined iron content and the expression of iron metabolism marker proteins transferrin receptor (TFR), divalent metal transporter 1 (DMT1), FTH, and ferroportin (FPN). Our results showed that lactoferrin alleviated iron overload induced by acute alcohol. The expression of TFR and DMT1 was downregulated, and FPN and FTH were upregulated after lactoferrin treatment in vivo and in vitro. Above all, the study suggested that lactoferrin can alleviate AALI by mitigating acute alcohol-induced ferroptosis. Lactoferrin may offer new strategies for the prevention or treatment of AALI., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Scope: Lactoferrin (LF) is an iron-bound protein with a molecular weight of about 80 kDa. LF has many biological functions such as antibacterial, antiviral, immunomodulatory, and anticancer. The purpose of this study is to explore the research trend of LF through bibliometric analysis., Methods and Results: The search is conducted in the Web of Science Core Collection database, and then the publications information of LF related literature is exported. Based on CiteSpace and VOSviewer software, countries, institutions, authors, journals, keywords, and so on are analyzed. Since 1987, a total of 9382 literature have been included, and the number of papers related to LF has increased year by year. These publications come mainly from 124 countries and 725 institutions. Of the 1256 authors analyzed, Valenti Piera is the one with the most publications. The burst strength of gut microbiota, antioxidant, nanoparticles, and in vitro digestion are 21.3, 15.63, 23.03, and 13.51, respectively. They represent the frontier of research in this field and are developing rapidly., Conclusion: This study shows that LF has important research value. The study of LF nanoparticles and the effects of LF on the gut microbiota are an emerging field that helps to explore new research directions., (© 2024 Wiley‐VCH GmbH.)

Lactoferrin (Lf), a multifunctional cationic glycoprotein extracted from milk or colostrum, is able to chelate two ferric ions per molecule, inhibit the formation of reactive oxygen species, interact with the anionic components of bacteria or host cells, and enter inside host cell nucleus, thereby exerting antibacterial, anti-invasive, and anti-inflammatory activities. By virtue of Lf presence, bovine colostrum is expected to perform analogous functions to pure Lf, along with additional activities attributable to other bioactive constituents. The present research aims to compare the antibacterial, anti-invasive, and anti-inflammatory activities of bovine Lf purified from milk (mbLf) and colostrum (cbLf) in comparison to those exhibited by whole bovine colostrum (wbc). The results demonstrated a major efficacy of mbLf in inhibiting pathogenic bacteria and in exerting anti-invasive and anti-survival activities with respect to cbLf and wbc. Furthermore, mbLf lowered IL-6 levels to those of uninfected cells, while a less evident decrease was observed upon cbLf treatment. Conversely, wbc managed to slightly lower IL-6 levels compared to those synthesized by infected cells. These data demonstrate that, to obtain maximum effectiveness in such activities, Lf should be formulated/used without addition of other substances and should be sourced from bovine milk rather than colostrum., Competing Interests: The authors declare no conflict of interest.

Hydroxychloroquine (HCQ), an antimalarial drug widely used in treating rheumatoid disorders. Many side effects have been reported with HCQ administration indicating its hazardous effects on various organs. No previous studies reported the effect of long-term administration of oral HCQ on pancreatic tissue. Our study assessed pancreatic tissues functional and histopathological alterations following prolonged oral administration of HCQ. We also investigated the possible ameliorative effects of the lactoferrin (LF) coadministration with HCQ in adult male albino rats. Forty adult male Wister albino rats were divided into: negative control, LF positive control (2 g/kg), HCQ-treated (200 mg/kg), and HCQ+LF treated. Biochemical, histological, immunohistochemical, and morphometric analyses of the pancreatic tissues were conducted. Our findings revealed that prolonged oral administration of HCQ induced significant disruption of the pancreatic acinar architecture, enlarged congested islets of Langerhans, and elevated plasma insulin, amylase, and lipase levels. Interestingly, LF administration ameliorated the deleterious effects of prolonged HCQ administration on pancreatic tissue of adult male albino rats. In conclusion, prolonged oral administration of HCQ induced pancreatic tissue damage in rats, while LF attenuates HCQ-induced pancreatic injury. Our results emphasized the necessity of prescribing HCQ with caution, considering both dosage and treatment duration., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Human milk lactoferrin (hmLF) is a glycoprotein with well-known effects on immune function. Helaina Inc. has used a glycoengineered yeast, Komatagaella phaffii, to produce recombinant human lactoferrin (Helaina rhLF, Effera™) that is structurally similar to hmLF with intended uses as a food ingredient. However, earlier FDA reviews of rhLF were withdrawn due to insufficient safety data and unanswered safety questions the experts and FDA raised about the immunogenicity/immunotoxicity risks of orally ingested rhLF. Helaina organized a panel of leading scientists to build and vet a safety study roadmap containing the studies and safety endpoints needed to address these questions. Panelists participated in a one-day virtual workshop in June 2023 and ensuing discussions through July 2023. Relevant workshop topics included physicochemical properties of LF, regulatory history of bovine LF and rhLF as food ingredients in the FDA's generally recognized as safe (GRAS) program, and synopses of publicly available studies on the immunogenicity/alloimmunization, immunotoxicology, iron homeostasis, and absorption, distribution, metabolism, and excretion of rhLF. Panelists concluded that the safety study roadmap addresses the unanswered safety questions and the intended safe use of rhLF as a food ingredient for adults and agreed on broad applications of the roadmap to assess the safety and support GRAS of other recombinant milk proteins with immunomodulatory functions., Competing Interests: Declaration of competing interest Carrie-Anne Malinczak, Anthony Clark, and Ross Peterson are employees of Helaina Inc. Leigh Ann Burns Naas, Michael DiNovi, Norbert Kaminski, Bo Lönnerdal, and Robert Merker have received honoraria and/or paid consultancy from Helaina Inc. Dietrich Conze and Claire Kruger are employed by Spherix and have received paid consultancy from Helaina Inc., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Autophagy is a new window of science that has been noticed due to the importance of specific therapies in cancer. In this study, the effect of lactoferrin (Lf) on the expression level of ATG101, mTOR and AMPK genes in breast cancer cell line MCF7, as well as the interaction between lactoferrin protein and their protein were investigated. The expression level of the genes was measured using a real-time PCR method. PDB, UniProt, KEGG, and STRING databases and ClusPro webserver and PyMol software were used in silico study. The results showed that the expression level of the ATG101 gene in treatment with concentrations of 100, 400, 600, and 800 μg/ml Lf decreased by 0.05, 0.13, 0.54 and 0.77, respectively. The expression level of the mTOR gene in treatment with concentrations of 100, 400, 600, and 800 μg/ml Lf decreased by 0.07, 0.05, 0.13, and 0.49 times respectively. The level of the AMPK gene expression in treatment with concentrations of 100, 400, 600, and 800 μg/ml Lf decreased by 0.05, 0.01, 0.06, and 0.03, respectively. Virtualization of the interaction of Lf protein with ATG101, mTOR and AMPK proteins by Pymol software showed that the N lobe region of Lf interacted with the HORMA domain of ATG101 protein, the fat domain of mTOR protein, and the CTD domain of AMPK protein. Although Lf was not able to increase the expression of autophagy-inducing genes, it may be able to induce autophagy through protein interaction by activating or inhibiting proteins related to autophagy regulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Postmenopausal dyspareunia and vulvar pain are common complaints, affecting about 60% of women within a few years after hormone levels begin to decline (such as estrogen and androgen). Atrophic changes mainly located in the vulvar vestibule and vulnerability to vulvovaginal infections in postmenopause could be predisposing factors to the development of vulvar burning/pain and introital dyspareunia (vestibulodynia secondary to atrophy). Tibolone is the most effective and safe alternative for treating menopausal symptoms. The role of Lactobacilli and lactoferrin shows its effectiveness in the treatment of vaginal microbiota dysbiosis. The aim of the present study was to assess the efficacy of the combination of tibolone and an oral-specific Lactobacilli mixture in combination with bovine lactoferrin as synergistic therapy for the treatment of vestibulodynia related to atrophy., Methods: In this study, we included 35 postmenopausal women with at least 1 year of amenorrhea, affected by vulvar burning/pain and introital dyspareunia. All participants received treatment with open-label, oral Tibolone 2.5 mg and Lactobacilli mixture (5 × 10 9 CFU per capsule) in combination with bovine lactoferrin (Respecta ® ). Each product was taken once daily for 90 days., Results: After 90 d of therapy with TIB+ Respecta ® , in 30 women that completed the treatment, there was a statistically significant decrease from the baseline in the mean of the Visual Analog Scale for vulvar burning/pain and a reduction in scores in the pain evaluation test., Conclusions: This study provides evidence that the combination of TIB+ Respecta ® was effective in reducing symptoms related to vestibular pain and hypersensitivity in a postmenopausal setting.

Introduction: Avian coccidiosis presents a significant challenge to the poultry industry in Egypt, highlighting the urgent need for validating new drug targets offering promising prospects for the development of advanced anticoccidials. Although numerous reports highlight the activity of lactoferrin (LF) against various microorganisms, its potential against Eimeria has not been explored. The present study evaluated the potential anticoccidial effect of LF and diclazuril in broiler chickens experimentally infected with Eimeria tenella ., Methods: A total of 100 one-day-old broiler chicks were divided into five equal groups (20 each) as follows: Group 1 (G1) served as the normal healthy control group, Group 2 (G2) consisted of chickens infected with 1 × 10 5 sporulated E. tenella oocysts at 14 days of age, Group 3 (G3) comprised infected chickens treated with diclazuril (0.5 mL/L in drinking water) for 3 days successively, Group 4 (G4) included infected chickens treated with LF (at a dose of 250 mg/kg of diet) from one day of age until the end of the study, and Group 5 (G5) comprised infected chickens treated with both LF and diclazuril., Results: The positive control group (G2) experienced significant reductions in body weight (BW), BW gain, serum glucose, lipase, amylase, total antioxidant capacity, several hematological indices, and total proteins, along with alterations in various antioxidant enzymes. Conversely, serum levels of aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatases (ALP), urea, creatinine, nitric oxide, mean corpuscular volume (MCV), White blood cells (WBCs), heterophils, alpha 2, beta 1, and liver contents of malondialdehyde were elevated in this group. Moreover, higher oocyst counts and lesion scores, along with histopathological alterations, were observed in G2. Remarkably, treatment with diclazuril and/or LF demonstrated potent antioxidant and anticoccidial effects, resulting in reduced shedding of oocysts, lesion scores, and lymphocytic infiltrates in the cecum. Additionally, these treatments improved the antioxidant and immune systems in chickens and restored all histopathological changes reported in the infected non-treated group (G2)., Conclusion: This study offers novel perspectives on the potential anticoccidial effects of the combination of LF and diclazuril in broiler chickens infected with E. tenella , highlighting the potential synergistic actions of LF in treating poultry coccidiosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Abd El Monsef, El Zohairy, Hassan, Salem, Gouda, Mansour, Alkhaldi, Alzaylaee and Elmahallawy.)

Lactoferrin (LF), a multifunctional glycoprotein found in mammalian milk and various exocrine secretions, plays a pivotal role in modulating various responses. Lactoferrin plays a significant role in type-2 diabetes by improving hepatic insulin resistance and pancreatic dysfunction however, the exact mechanism for this improvement is not thoroughly elucidated. To this date, there are no evidence that attributes the direct interaction of lactoferrin with components of NF-κB pathway. Considering this precedent, the current study aimed to investigate the interaction of LF with key components of NF-κB pathway using molecular docking and simulation approaches. Results indicated that LF has shown highly stable interactions with IL-1β, IL-6, IκBα and NF-κB, and relatively weaker interactions with IKK and TNF-α. All four trajectories, including root mean square of deviations (RMSD), root mean square of fluctuation (RMSF), hydrogen bond interactions, and radius of gyration (RoG), confirmed the stable interactions of LF with NF-κB pathway components. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analysis further supports their stable interactions. To the best of our knowledge, this is the first study to provide convincing evidence that LF can interact with all six major components of the NF-κB pathway. This study provides pioneering in-silico evidence that lactoferrin (LF) can interact with all six major components of the NF-κB pathway, demonstrating highly stable interactions with IL-1β, IL-6, IκBα, and NF-κB, and relatively weaker interactions with IKK and TNF-α. These findings suggest that LF and its peptides have significant potential for both preventive and therapeutic applications by targeting the NF-κB pathway to inhibit inflammation, thereby improving insulin sensitivity and aiding in the management of diabetes., Competing Interests: The authors of this manuscript declared that they have no potential conflict of interest., (© 2024 The Authors. Published by Elsevier Ltd.)

To develop novel bovine lactoferrin (bLF) peptides targeting bLF-tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6) binding sites, we identified two peptides that could target bLF-TRAF6 binding sites using structural analysis. Moreover, another peptide that could bind to the TRAF6 dimerization area was selected from the bLF sequence. The effects of each peptide on cytokine expression in lipopolysaccharide (LPS)-stimulated osteoblasts (ST2) and on osteoclastogenesis were examined using an LPS-treated co-culture of primary bone marrow cells (BMCs) with ST2 cells and a single culture of osteoclast precursor cells (RAW-D) treated with soluble receptor activator of NF-κB ligand. Finally, the effectiveness of these peptides against LPS-induced alveolar bone destruction was assessed. Two of the three peptides significantly suppressed LPS-induced TNF-α and interleukin-1β expression in ST2 cells. Additionally, these peptides inhibited and reversed LPS-induced receptor activator of NF-κB ligand (RANKL) upregulation and osteoprotegerin (OPG) downregulation, respectively. Furthermore, both peptides significantly reduced LPS-induced osteoclastogenesis in the BMC-ST2 co-culture and RANKL-induced osteoclastogenesis in RAW-D cells. In vivo, topical application of these peptides significantly reduced the osteoclast number by downregulating RANKL and upregulating OPG in the periodontal ligament. It is indicated that the novel bLF peptides can be used to treat periodontitis-associated bone destruction., (© 2024 The Author(s). Chemical Biology & Drug Design published by John Wiley & Sons Ltd.)

The oral toxicity of recombinant human lactoferrin (rhLF, Helaina rhLF, Effera™) produced in Komagataella phaffii was investigated in adult Sprague Dawley rats by once daily oral gavage for 14 consecutive days. The study used groups of 3-6 rats/sex/dose. The vehicle control group received sodium citrate buffer, and the test groups received daily doses of 200, 1000, and 2000 mg of rhLF in sodium citrate buffer per kg body weight. Bovine LF at 2000 mg/kg body weight per day was used as a comparative control. Clinical observations, body weight, hematology, clinical chemistry, iron parameters, immunophenotyping, and gross examination at necropsy were used as criteria for detecting the effects of treatment in all groups and to help select dose levels for future toxicology studies. Quantitative LF levels were also analyzed as an indication of bioavailability. Overall, administration of Helaina rhLF by once daily oral gavage for 14 days was well tolerated in rats at levels up to 2000 mg/kg/day, or 57 × Helaina's intended commercial use in adults, and indicating that a high dose of 2000 mg/kg/day is appropriate for future definitive toxicology studies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Authors RP, JSS, BF, RV-D, AJC, and C-AM are all employees of Helaina, Inc.

Lactoferrin is an antimicrobial glycoprotein that demonstrates a broad-spectrum of activity against a wide variety of clinical pathogens. This study investigated the potential of bovine lactoferrin (bLf) against multidrug resistant Staphylococcus capitis (S. capitis) strains. Growth curve analysis and time-kill curves demonstrated that at 750 µg ml-1 lactoferrin significantly inhibited (50.6%, P < 0.05) the growth of most isolates tested (90%), and this effect was based on a bacteriostatic mechanism. At the same concentration, bLf also significantly inhibited (30%, P < 0.05) biofilm formation in 40% of strains tested. Combinations of bLf with selected antibiotics were assessed for enhanced antimicrobial activity using growth curves. BLf combined with β-lactam antibiotics reduced the growth of S. capitis strains, however, the effects were not significant. BLf displays antimicrobial effects against multidrug resistant S. capitis isolates, but with strain-specific effects., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Immune deficiency is a prevalent issue among kittens, severely threatening their health and development by increasing susceptibility to infections and diseases. This study investigates the effects of dietary supplements containing lactoferrin and Lactobacillus plantarum ( L. plantarum ) on the immune function, intestinal health, and microbiota composition of kittens. The results demonstrate that these supplements significantly enhance immune responses, with immunoglobulin A (IgA) levels increasing by 14.9% and IgG levels by 14.2%. Additionally, there was a notable 28.7% increase in catalase activity, indicating a reduction in oxidative stress. Gastrointestinal (GI) health improved markedly, evidenced by increased populations of beneficial bacteria such as Lactobacillus , which rose from 4.13% to 79.03% over the study period. The DNC group also showed significant reductions in pro-inflammatory cytokines, including decreases of 13.94% in IL-2, 26.46% in TNF-α, and 19.45% in IFN-γ levels. Furthermore, improvements in physical conditions were observed, including enhanced coat condition and mental status. These findings underline the potential of lactoferrin and L. plantarum as effective dietary interventions to improve kitten health, thereby reducing dependency on antibiotics and mitigating associated risks. This research provides a scientific foundation for optimizing nutritional management practices to enhance the overall vitality of kittens during their critical growth phases.

Lactoferrin (LAC) is an iron-binding glycoprotein found in mammalian secretion, such as milk and colostrum, which has several advantageous biological characteristics, such as antioxidant and antimicrobial activity, intestinal iron absorption and regulation, growth factor activity, and immune response. LAC is an active GRAS food ingredient and can be included in the food packaging/film matrix in both free and encapsulated forms to increase the microbial, mechanical, barrier, and thermal properties of biopolymer films. Additionally, LAC-containing films maintain the quality of fresh food and extend the shelf life of food products. This paper primarily focuses on examining how LAC affects the antimicrobial, antioxidant, physical, mechanical, thermal, and optical properties of packaging films. Moreover, the paper explains the attributes of films incorporating LAC within different matrices, exploring the interaction between LAC and polymers. The potential of LAC-enhanced food packaging technologies is highlighted, showcasing their promising applications in sustainable food packaging., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Noncovalent interactions of 4 selected phenolic acids, including gallic acid (GA), caffeic acid (CA), chlorogenic acid (CGA), and rosmarinic acid (RA) with lactoferrin (LF) were investigated. Compound combined with LF in the binding constant of CA > GA > RA > CGA, driven by van der Waals and hydrogen bonding for GA, and hydrophobic forces for others. Conformation of LF was affected at secondary and ternary structure levels. Molecular docking indicated that GA and CA located in the same site near the iron of the C-lobe, whereas RA and CGA bound to the C2 and N-lobe, respectively. Significantly enhanced antioxidant activity of complexes was found compared with pure LF, as demonstrated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis(2-ethylbenzothiazoline-6-sulfonate) (ABTS), and ferric reducing antioxidant power (FRAP) models. Caffeic acid, CGA, and RA significantly decreased the emulsifying stability index and improved foam ability of LF, and the effect of CA and RA was the most remarkable, respectively., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

This study explored the relationship between the interfacial behavior of lactoferrin-(-)-epigallocatechin-3-gallate covalent complex (LF-EGCG) and the stability of high internal phase Pickering emulsions (HIPPEs). The formation of covalent bond between lactoferrin and polyphenol was verified by the increase in molecular weight. In LF-EGCG group, the surface hydrophobicity, interfacial pressure, and adsorption rate were decreased, while the molecular flexibility, interfacial film viscoelasticity, and interfacial protein content were increased. Meanwhile, LF-EGCG HIPPE possessed reduced droplet size, increased ζ-potential and stability. Rheology showed the viscoelasticity, structural recovery and gel strength of LF-EGCG HIPPE were improved, giving HIPPE inks better 3D printing integrity and clarity. Moreover, the free fatty acids (FFA) release of LF-EGCG HIPPE (62.6%) was higher than that of the oil group (50.1%). Therefore, covalent treatment effectively improved the interfacial properties of protein particles and the stability of HIPPEs. The macroscopic properties of HIPPEs were positively regulated by the interfacial properties of protein particles. The result suggested that the stability of emulsions can be improved by regulating the interfacial properties of particles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This study aimed to develop complex coacervates utilizing lactoferrin (LF) and chia seed mucilage (CSM) for promoting intestinal delivery of quercetin (Q) and fortification of set yogurt. Three cross-linkers, including calcium chloride (CC), transglutaminase (TG), and polyphenolic complex (HP), were used to further reinforce the coacervate network. Cross-linked coacervates had higher values of coacervate yield, encapsulation efficiency, and loading capacity. They efficiently preserved Q under gastric condition (⁓87%-99%), with CSM-TG-Q-LF being most effective for intestinal delivery of Q. Moreover, digested pellets of the cross-linked coacervates displayed better antioxidant activity than the uncross-linked coacervates with CSM-TG-Q-LF pellets showing maximum bioactivity. The Q-loaded coacervates demonstrated superior assembly in the yogurt matrix compared to the unencapsulated Q. Moreover, the coacervate systems, especially CSM-TG-Q-LF significantly improved the textural properties of yogurt and the stability of Q in it. Therefore, CSM-TG-LF is a promising carrier to promote intestinal delivery and food application of hydrophobic molecules., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study explored the impact of homogenization (at pressures of 16, 30, and 45 MPa) on both raw and high hydrostatic pressure (HHP)-treated human milk (HM). It focused on protein compositions and binding forces of soluble and insoluble fractions for both milk fat globule membrane (MFGM) and skim milk. Mild homogenization of HHP-treated milk increased lactoferrin (LF) levels in the insoluble fractions of both MFGM and skim milk, due to insoluble aggregation through hydrophobic interactions. Intense homogenization of HHP-treated milk decreased the LF level in the MFGM fractions due to the LF desorption from the MFGM, which increased LF level in the insoluble skim milk fraction. Homogenized-HHP treated milk showed noticeably higher casein (CN) level at the MFGM compared to homogenized-raw milk, attributed to HHP effect on CN micelles. Overall, the combined use of HHP and shear-homogenization should be avoided as it increased the biological proteins in insoluble fractions., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. DATA AVAILABILITY. Data will be made available on request., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Lactoferrin (LF) with various biological functions demonstrates great application potential. However, its application was restricted by its poor gelation and instability. The aim of this work was to explore the effect of microbial transglutaminase (MTGase) and Tremella fuciformis polysaccharide (TP) on the functional properties of LF. The formation of a self-supporting LF gel could be induced by MTGase through generating covalent crosslinks between the LF protein molecules. Meanwhile, TP was introduced into the gel system to improve the strength of LF-TP composite gels by enhancing non-covalent interactions such as hydrogen bond and electrostatic interactions during gel formation. Additionally, the LF-TP composite gel exhibited outstanding functional characteristics such as gastrointestinal digestive stability and antioxidant property. This work clarified the mechanism on MTGase and TP-mediated modification of lactoferrin, offered a novel strategy to increase the functional characteristics of LF, and enlarged the application range of LF and TP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Multiple sclerosis is a chronic inflammatory demyelinating disorder of the CNS characterized by continuous myelin damage accompanied by deterioration in functions. Clobetasol propionate (CP) is the most potent topical corticosteroid with serious side effects related to systemic absorption. Previous studies introduced CP for remyelination without considering systemic toxicity. This work aimed at fabrication and optimization of double coated nano-oleosomes loaded with CP to achieve brain targeting through intranasal administration. The optimized formulation was coated with lactoferrin and chitosan for the first time. The obtained double-coated oleosomes had particle size (220.07 ± 0.77 nm), zeta potential (+30.23 ± 0.41 mV) along with antioxidant capacity 9.8 μM ascorbic acid equivalents. Double coating was well visualized by TEM and significantly decreased drug release. Three different doses of CP were assessed in-vivo using cuprizone-induced demyelination in C57Bl/6 mice. Neurobehavioral tests revealed improvement in motor and cognitive functions of mice in a dose-dependent manner. Histopathological examination of the brain showed about 2.3 folds increase in corpus callosum thickness in 0.3 mg/kg CP dose. Moreover, the measured biomarkers highlighted the significant antioxidant and anti-inflammatory capacity of the formulation. In conclusion, the elaborated biopolymer-integrating nanocarrier succeeded in remyelination with 6.6 folds reduction in CP dose compared to previous studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To examine how reduced iron content and added bovine lactoferrin in infant formula affect the antibody response following routine immunisation., Methods: In this randomised controlled trial, 180 Swedish formula-fed infants received, from 6 weeks to 6 months of age, a 2 mg/L iron formula with (n = 72) or without (n = 72) bovine lactoferrin, or a control formula with 8 mg/L iron and no lactoferrin (n = 36). Another 72 infants were recruited as a breastfed reference. Serum immunoglobulin G (IgG) levels against Haemophilus influenzae type b (Hib), diphtheria and tetanus were assessed at four, six and 12 months of age., Results: With an equal gender distribution, 180 + 72 term infants were included with a mean age of 7.0 ± 0.7 weeks. At 12 months, infants fed low iron formula showed a significantly higher geometric mean Hib IgG (1.40 μg/mL [1.07-1.83]) compared to the control formula infants (0.67 μg/mL [0.42-1.07]). For all three vaccines, breastfed infants had significantly lower IgG levels at six and 12 months of age., Conclusion: Except for higher Hib IgG levels at 12 months in infants fed low iron formula, the interventions did not affect vaccine IgG response. Unexpectedly, breastfed infants had significantly lower vaccine IgG levels compared to formula-fed infants., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

In this work, lactoferrin (LF)-chitosan (CS) composite hydrogels with good loading capacity of thermosensitive bioactive substances were successfully obtained by microbial transglutaminase (MTG)-induced cross-linking. We evaluated the rheological, textural, and microstructural characteristics of the composite hydrogels under different conditions. The results demonstrated that the concentrations of LF and CS as well as the amount of MTG could regulate the textural properties, rheological properties, and water holding capability. The results of FTIR and fluorescence spectroscopy indicated that the main interactions within the composite gel were hydrogen and isopeptide bonds. Additionally, in vitro digestion simulation results verified that riboflavin kept stable in stomach due to the protection of LF-CS composite hydrogels and was released in small intestine. These results suggested that thermosensitive bioactive substance could be encapsulated and delivered by the LF-CS composite hydrogel, which could be applied in lots of potential applications in functional food as a new material.

Human lactoferrin (HLF), an essential nutrient found in breast milk, possesses antibacterial, anti-inflammatory, and immune-enhancing properties. In this study, the effects of three constitutive promoters (P 21 , P 43 , and P veg ) and three inducible promoters (P grac100 , P xylA , and P tet * ) on the expression of HLF were compared using Bacillus subtilis G601 as the host strain. The results showed that the highest expression of HLF, reaching 651.57 μg/L, was achieved when regulated by the P tet * promoter. Furthermore, the combinational optimization of ribosome binding site (RBS) and signal peptides was investigated, and the optimal combination of RBS6 and SP yycP resulted in increased HLF expression to 1 099.87 μg/L, with 498.68 μg/L being secreted extracellularly. To further enhance HLF secretion, the metal cations-related gene dltD was knocked out, leading to an extracellular HLF level of 637.28 μg/L. This study successfully demonstrated the secretory expression of HLF in B . subtilis through the selection and optimization of expression elements, laying the foundation for the development of efficient B . subtilis cell factories for lactoprotein synthesis.

The lack of specific biological materials and biomarkers limits our knowledge of the mechanisms underlying intrauterine regulation of iron supply to the fetus. Determining the meconium content of proteins commonly used in the laboratory to assess the transport, storage, and distribution of iron in the body may elucidate their roles in fetal development. Ferritin, transferrin, haptoglobin, ceruloplasmin, lactoferrin, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), and calprotectin were determined by ELISA in meconium samples obtained from 122 neonates. There were strong correlations between the meconium concentrations of haptoglobin, transferrin, and NGAL ( p < 0.05). Meconium concentrations of ferritin were several-fold higher than the concentrations of the other proteins, with the exception of calprotectin whose concentration was approximately three-fold higher than that of ferritin. Meconium ceruloplasmin concentration significantly correlated with the concentrations of MPO, NGAL, lactoferrin, and calprotectin. Correlations between the meconium concentrations of haptoglobin, transferrin, and NGAL may reflect their collaborative involvement in the storage and transport of iron in the intrauterine environment in line with their recognized biological properties. High meconium concentrations of ferritin may provide information about the demand for iron and its utilization by the fetus. The associations between ceruloplasmin and neutrophil proteins may indicate the involvement of ceruloplasmin in the regulation of neutrophil activity in the intrauterine environment., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Background: Sarcopenia is an age-related condition characterized by progressive loss of muscle mass, strength, and function. The occurrence of sarcopenia has a huge impact on physical, psychological, and social health. Therefore, the prevention and treatment of sarcopenia is becoming an important public health issue., Method: 35 six-week-old male C57BL/6 mice were randomly divided into five groups, one of which served as a control group, while the rest of the groups were constructed as a model of sarcopenia by intraperitoneal injection of D-galactose. The intervention with lactoferrin, creatine, and their mixtures, respectively, was carried out through gavage for 8 weeks. Muscle function was assessed based on their endurance, hanging time, and grip strength. The muscle tissues were weighed to assess the changes in mass, and the muscle RNA was extracted for myogenic factor expression and transcriptome sequencing to speculate on the potential mechanism of action by GO and KEGG enrichment analysis., Result: The muscle mass (lean mass, GAS index), and muscle function (endurance, hanging time, and grip strength) decreased, and the size and structure of myofiber was smaller in the model group compared to the control group. The intervention with lactoferrin and creatine, either alone or combination, improved muscle mass and function, restored muscle tissue, and increased the expression of myogenic regulators. The combined group demonstrated the most significant improvement in these indexes. The RNA-seq results revealed enrichment in the longevity-regulated pathway, MAPK pathway, focal adhesion, and ECM-receptor interaction pathway in the intervention group. The intervention group may influence muscle function by affecting the proliferation, differentiation, senescence of skeletal muscle cell, and contraction of muscle fiber. The combined group also enriched the mTOR-S6K/4E-BPs signaling pathway, PI3K-Akt signaling pathway, and energy metabolism-related pathways, including Apelin signaling, insulin resistance pathway, and adipocytokine signaling pathway, which affect energy metabolism in muscle., Conclusions: Lactoferrin and creatine, either alone or in combination, were found to inhibit the progression of sarcopenia by influencing the number and cross-sectional area of muscle fibers and muscle protein synthesis. The combined intervention appears to exert a more significant effect on energy metabolism.

Modern functional foods are designed to provide health benefits beyond basic nutrition. They are enriched with bioactive ingredients like probiotics, vitamins, minerals, and antioxidants. These foods support overall health, enhance immune function, and help prevent chronic diseases. Milk proteins and tea are known to influence satiety and regulate body weight. Studies have shown that green tea polyphenols, namely, (-)-epigallocatechin gallate (EGCG), and whey proteins, predominantly lactoferrin (LF) from milk, play a role in regulating satiety. This study aims to investigate the effect of conjugating EGCG with apo-lactoferrin (Apo-LF) and assessing these effects on satiety through monitoring glucagon-like peptide-1 (GLP-1) regulation in a human colon (NCI-H716) cell line. Apo-LF-EGCG conjugates were synthesized and characterized in terms of structural and functional properties. The effect on GLP-1 regulation was assessed by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) to monitor gene and protein expressions, respectively. The results revealed that the protein-polyphenol interaction occurs through the complex formation of hydrogen bonds at the O-H and carbonyl groups of EGCG. The conjugates also showed a significant up-regulation of gene and protein expression levels of GLP-1 while also preventing EGCG from degradation, thereby preserving its antioxidant properties. The Apo-LF-EGCG conjugates increase satiety via increasing GLP-1 secretion in human colon cells while simultaneously retaining the antioxidant properties of EGCG. Therefore, these conjugates show potential for use as dietary supplements to enhance satiety.

The prevalence of allergic diseases has dramatically increased among children in recent decades. These conditions significantly impact the quality of life of allergic children and their families. Lactoferrin, a multifunctional glycoprotein found in various biological fluids, is emerging as a promising immunomodulatory agent that can potentially alleviate allergic diseases in children. Lactoferrin's multifaceted properties make it a compelling candidate for managing these conditions. Firstly, lactoferrin exhibits potent anti-inflammatory and antioxidant activities, which can mitigate the chronic inflammation characteristic of allergic diseases. Secondly, its iron-binding capabilities may help regulate the iron balance in allergic children, potentially influencing the severity of their symptoms. Lactoferrin also demonstrates antimicrobial properties, making it beneficial in preventing secondary infections often associated with respiratory allergies. Furthermore, its ability to modulate the immune response and regulate inflammatory pathways suggests its potential as an immune-balancing agent. This review of the current literature emphasises the need for further research to elucidate the precise roles of lactoferrin in allergic diseases. Harnessing the immunomodulatory potential of lactoferrin could provide a novel add-on approach to managing allergic diseases in children, offering hope for improved outcomes and an enhanced quality of life for paediatric patients and their families. As lactoferrin continues to capture the attention of researchers, its properties and diverse applications make it an intriguing subject of study with a rich history and a promising future.

Breast milk contains numerous factors that are involved in the maturation of the immune system and development of the gut microbiota in infants. These factors include transforming growth factor-β1 and 2, immunoglobin A, and lactoferrin. Breast milk factors may also affect epidermal differentiation and the stratum corneum (SC) barrier in infants, but no studies examining these associations over time during infancy have been reported. In this single-center exploratory study, we measured the molecular components of the SC using confocal Raman spectroscopy at 0, 1, 2, 6, and 12 months of age in 39 infants born at our hospital. Breast milk factor concentrations from their mothers' breast milk were determined. Correlation coefficients for the two datasets were estimated for each molecular component of the SC and breast milk factor at each age and SC depth. The results showed that breast milk factors and molecular components of the SC during infancy were partly correlated with infant age in months and SC depth, suggesting that breast milk factors influence the maturation of the SC components. These findings may improve understanding of the pathogenesis of skin diseases associated with skin barrier abnormalities.

Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate. The present study was to develop lactoferrin-modified liposomal etomidate (Eto-lip-LF) for enhanced drug distribution in the brain and improved anesthetic effects. Eto-lip-LF had good stability for storage and hemocompatibility for intravenous injection. Compared with the non-lactoferrin-containing liposomes, the lactoferrin-modified liposomes had notably enhanced brain-targeting ability in vivo, which was probably realized by the binding of transferrin with the transferrin and lactoferrin receptors highly distributed in the brain. Eto-lip-LF had a therapeutic index of about 25.3, higher than that of many other general anesthetics. Moreover, compared with the commercial etomidate emulsion, Eto-lip-LF could better achieve rapid onset of general anesthesia and rapid recovery from anesthesia, probably due to the enhanced drug delivery to the brain. The above results demonstrated the potential of this lactoferrin-modified liposomal etomidate to become an alternative preparation for clinical general anesthesia.

The growth of Lactobacillus plantarum , a member of the Lactobacillus genus, which plays a crucial role in the bacterial microbiome of the gut, is significantly influenced by manganese ions. They can be safely delivered to the intestines by exploiting the chelating abilities of lactoferrin. The aim of this work was to encapsulate lactoferrin saturated with manganese ions (MnLf) in a system based on the Eudragit ® RS polymer to protect protein from degradation and manganese release in the gastric environment. The entrapment efficiency was satisfactory, reaching about 95%, and most importantly, manganese ions were not released during microparticles (MPs) formation. The release profile of the protein from the freshly prepared MPs was sustained, with less than 15% of the protein released within the first hour. To achieve similar protein release efficiency, freeze-drying was carried out in the presence of 10% ( w / v ) mannitol as a cryoprotectant for MPs frozen at -20 °C. MPs with encapsulated MnLf exhibited prebiotic activity towards Lactobacillus plantarum . More importantly, the presence of equivalent levels of manganese ions in free form in the medium, as well as chelating by lactoferrin encapsulated in MPs, had a similar impact on stimulating bacterial growth. This indicates that the bioavailability of manganese ions in our prepared system is very good.

Telogen effluvium is characterized by excessive hair shedding usually following a stressful event. Ferritin has been used in clinical practice as a biomarker of nonanemic iron deficiency in cases of telogen effluvium. During the years of the COVID19 pandemic, telogen effluvium was reported as a part of post covid manifestations. As ferritin was also a biomarker for inflammation in cases with covid infection, this study was designed to evaluate the value of ferritin in cases with postcovid telogen effluvium one hundred patients recovering from covid 19 for 4-12 weeks were included in the study, detailed drug and laboratory history was obtained and serum ferritin level was measured. the mean serum level of ferritin among telogen effluvium patients was significantly lower than controls (68.52 ± 126 and 137 ± 137.597 ug/L respectively). Patients with telogen effluvium used significantly more azithromycin and ivermectin and significantly less vitamin C, D, lactoferrin and zinc than the controls Although serum ferritin is lower among telogen effluvium patients, it was still higher than the cutoff value for diagnosing nonanemic iron deficiency, we suggest that it will not be a good biomarkers in these cases. Our secondary outcomes showed that dietary supplements used during active infection such as vitamin C, D, lactoferrin and zinc might have a preventive value on postcovid hair loss, while azithromycin and ivermectin could have a negative long term effect on telogen effluvium., (© 2024. The Author(s).)

It is said that a wide range of renal functions are at risk from arsenic exposure. We examined how lactoferrin administration may mitigate inflammation, apoptosis, redox imbalance, and fibrosis in order to counteract arsenic-induced nephrotoxicity. Accordingly, male C57BL/6 mice (6 weeks) were divided into six experimental groups with six mice in each group. The first and second groups were intragastrically administered normal saline and sodium arsenite (NaAsO 2 ) at 5 mg/kg body weight concentrations as the negative control (NC) and NaAsO 2 groups. The third, fourth, and fifth groups were intragastrically administered lactoferrin at concentrations of 100, 200, and 400 mg/kg body weight in addition to NaAsO 2 at concentrations of 5 mg/kg body weight. The sixth group was intragastrically administered lactoferrin at a concentration of 200 mg/kg body weight with the experimental group set as the lactoferrin group. After daily drug administration for 4 weeks, the lactoferrin concentrations were optimized based on the results of renal index and renal function. Histopathological, biochemical, and gene expression analyses were performed to evaluate the status of renal tissue architecture, redox imbalance, inflammation, apoptosis, and fibrosis to confirm the alleviative effect of lactoferrin treatment against the NaAsO 2 exposure-induced nephrotoxicity. The results confirmed that the 200 mg/kg lactoferrin treatment mitigated these arsenic effects and maintained the normal renal frameworks. Conclusively, disrupting the renal redox balance and triggering inflammation, apoptosis, along with fibrosis is a milieu that arsenic, robustly exerts its nephrotoxic effect. Lactoferrin, probably by its direct and indirect control mechanism on these said pathways, can mitigate the nephrotoxicity and preserve the normal renal health., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aim: Recently, noninvasive fecal markers have been used as indicators of intestinal inflammation in patients with inflammatory bowel disease (IBD). We conducted a clinical validation study to measure fecal calprotectin (Cp), lactoferrin (Lf), and hemoglobin (Hb) levels using an all-in-one kit in patients with IBD and colorectal tumors and aimed to clarify the utility of these fecal markers., Methods: In this study, 104 patients were analyzed, including 25 patients with ulcerative colitis (UC), 20 with Crohn's disease (CD), 48 with colorectal tumors, and 13 healthy controls (HC). Of the 48 patients with colorectal tumors, 14 had invasive cancer. We validated the utility of fecal Cp, Lf, and Hb levels by simultaneously measuring fecal markers in patients with IBD and colorectal tumors., Results: Fecal Cp and Lf had almost equivalent abilities in detecting clinical remission in patients with UC; however, fecal Cp was slightly superior to Lf. Regarding colorectal tumors, fecal Cp and Lf levels tended to be higher in patients with adenomas and colorectal cancer than in HCs. Although fecal Hb alone had the best sensitivity and specificity for detecting colorectal cancer, it had relatively low sensitivity for detecting advanced neoplasms and colorectal cancer., Conclusion: Fecal Cp and Lf can be used as almost equivalent biomarkers to assess the clinical activity in patients with UC. Fecal Hb is the most useful marker for screening colorectal cancer; however, adding fecal Cp and Lf may compensate for the low sensitivity of detecting for advanced colorectal tumors based on Hb alone., (© 2024 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The free radical and cytokine statuses of the cornea during its thermal burn and the possibility of its correction by lactoferrin have been studied in Soviet Chinchilla rabbits. The development of a corneal thermal burn was accompanied by the development of oxidative stress (increased levels of TBA-reactive substances and carbonyl derivatives of proteins, decreased activity of SOD and GPx enzymes) and a pronounced inflammatory reaction with increased levels of TNF-1α, IL-10, TGF-1β. The use of lactoferrin had a pronounced therapeutic effect, which was manifested by accelerated healing, prevention of the development of complications (corneal perforations), a decrease in the severity of oxidative stress, an increase in the concentrations of TNF-1α (in the early stages), IL-10 (in the later stages), TGF-1β (throughout the experiment). At the same time, by the end of regeneration more severe corneal opacification was recognized compared to the control group. This may be associated with an increased level of anti-inflammatory cytokines, especially TGF-1β.